title: Interactions between alveolar macrophage subpopulations modulate their migratory function.
abstract: To better understand the mechanisms by which alveolar macrophages (AM) are attracted to local sites in the lung, the locomotion of AM in response to N-formyl-methionyl-leucyl-phenylalanine (FMLP) was investigated. Total bronchoalveolar cells (99% AM) obtained by a nondiscriminating bronchoalveolar lavage procedure migrated toward FMLP over a range of concentrations of 10(-12) M to 10(-6) M. Dose-response experiments showed a biphasic response with two peaks of migration obtained respectively at 5 x 10(-10) M and 10(-8) M. Analysis in the presence and absence of a positive gradient of FMLP revealed that the first peak of migration (5 x 10(-10) M FMLP) corresponded predominantly to chemotactic activity whereas the second peak of migration (10(-8) M FMLP) was associated with chemokinetic activity. To further evaluate these activities of oriented (chemotaxis) vs. random (chemokinesis) migration, AM were separated into two fractions by a two-step bronchoalveolar lavage procedure. Whereas fraction 1 displayed exclusively chemokinesis in response to higher concentrations of FMLP (10(-8) M), fraction 2 was totally unresponsive to FMLP over a wide range of concentrations (5 x 10(-11) M - 10(-7) M). When both fractions were combined, however, the chemotactic response to low concentrations of FMLP (5 x 10(-10) M) was restored. Additional analysis of these two AM fractions indicated that fraction 1 AM had a significantly lower degree of adherence and aggregation than fraction 2 AM. These data suggest that cell-cell cooperation is important for AM chemotactic response to FMLP and that such interaction may involve changes in adherence and aggregation.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Ottawa, Ontario, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Laplante
authors.forename: I
authors.initials: I
authors.lastname: Lemaire
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D008297:Male; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000166:cytology; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D009240:N-Formylmethionine Leucyl-Phenylalanine